Neuropathology of phenylacetate poisoning in rats: An experimental model of phenylketonuria

Wen, Gen; Wı́sniewski, Henryk M.; Shek, J.W.; Loo, Y. H.; Fulton, Thomas R.

doi:10.1002/ana.410070609

Cited by 42 publications

(14 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, a reduction in the genesis of membrane compartments prior to the 14th postnatal day is likely. Results of studies on the development of the cerebellum [13,33,41] and of the eye [41] in control and PA rats are also indicative of a developmen tal lag in PA animals.…”

Section: Synaptic Developmentmentioning

confidence: 98%

“…Since the brains of undernourished rats have a de creased content of DNA and protein, which has not been observed in PA rats [41], under nutrition is probably not a causative factor in the brain weight findings.…”

Section: Somatic Considerationsmentioning

confidence: 98%

“…Based on the model devised by Wen et al [41], the following dosage regime was used: 1.5 ¿imol/gBW on days3-8,2.5 /urnol/g BW on days 9-15, and 3.5 /¿mol/g BW on days 16-20. The volume of saline administered to control animals was equivalent to the volume of the PA solution injected into treated rats for a specific BW and dosage level.…”

Section: Methodsmentioning

confidence: 99%

“…The suckling rats were injected intraperitoneally with either PA or 0.9% saline (control), twice daily, the injections being 7 h apart [41], For the PA solution, phenylacetic acid (Unilab) and NaOH (Univar) were dis solved in a warmed solution of 0.9% saline. Based on the model devised by Wen et al [41], the following dosage regime was used: 1.5 ¿imol/gBW on days3-8,2.5 /urnol/g BW on days 9-15, and 3.5 /¿mol/g BW on days 16-20.…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

A Quantitative Ultrastructural Study of the Effects of Phenylacetate on Synaptic Organization in the Developing Rat Cerebral Cortex

Oorschot¹,

Jones²

1983

Dev Neurosci

View full text Add to dashboard Cite

Male rats were injected with either phenylacetate (PA; a phenylalanine metabolite) or saline (control). Osmicated tissue from the parietal cortex was analyzed qualitatively and quantitatively, attention being focused on possible synaptic changes in the molecular layer. PA-treated rats differed from controls in the following ways: a 20% decrease in body weight at 21 days, and a reduction in brain weight at 10 and 21 days; the presence of 'atypical' profiles (possibly derived from axonal growth cones) in the neuropil; a lag in the accretion of synapses per 100 μm² of tissue, and of vesicles per μm²of presynaptic terminal; the presence of a 'crossover' in the developmental trend for several synaptic organizational parameters between days 15 and 21; an elevation in synaptic density at day 21; an increased proportion of negatively curved synapses at 21 days; a significant difference in the preponderance of axodendritic synapses over days 7–21. This suggests that the metabolism of some neurons in the PA brain is initially different from normal, with a lag in synaptic development being evident. The increase in synaptic density and the relative preponderance of other synaptic parameters at 21 days signifies that an initial lag in development may alter the developmental scheme. This may be coupled with changes in synaptic efficacy and connectivity.

show abstract

Section: Synaptic Developmentmentioning

confidence: 98%

Section: Somatic Considerationsmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

A Quantitative Ultrastructural Study of the Effects of Phenylacetate on Synaptic Organization in the Developing Rat Cerebral Cortex

Oorschot¹,

Jones²

1983

Dev Neurosci

View full text Add to dashboard Cite

show abstract

“…Cerebellar hypoplasia can be marked in ADSL, although atrophy may extend to cerebrum and corpus callosum, and hyperphenylalaninemia is especially toxic (Poretti, Boltshauser, and Doherty 2014;Van den Berghe, Vincent, and Jaeken 1997;Wen et al 1980). The list of genetics mutations with comorbid ASD is too extensive to discuss in detail here.…”

Section: Other Genetic Disorders Comorbid With Asdmentioning

confidence: 99%

A theory inspired proposal for a novel medical treatment in autism. The cerebellar model of autism and the hypothesis of dorsal stream dysfunction: evidence from idiopathic and syndromic cases.

Vakalopoulos¹

2017

Preprint

View full text Add to dashboard Cite

The cerebellum figures prominently in the pathophysiology of idiopathic autism. Many syndromic comorbid cases and animal studies also highlight cerebellar involvement. The role of the cerebellum is implicated in cognitive and affective disorders. However, there remains a profound gap in understanding the route from genes, the effect of mutations on Purkinje cells and ultimately the behavioural phenotype. Given that conditions like autism are disorders of consciousness it is likely that progress will be made beyond the data generating enterprise, by improved theoretical models of the mind-body gap. A way forward is the proposal of consciousness as embodiment of a process of world discovery through motor efference copy. The cerebellum and basal ganglia are essential to a component theory of motor efference copy, providing a heuristic for understanding the structure of cortical dorsal and ventral stream pathways of a sensory modality. This then, further suggests that autism results from a selective dorsal stream dysfunction with all the attendant and hierarchical features that follow such a model and lead to both high level social and attentional deficits as well as lower level motor and restrictive interests. The paper aims to present evidence for dorsal stream dysfunction and how it may relate to a primary cerebellar pathology. The involvement of the cerebellum in most if not all syndromic cases of comorbid ASD is then presented. Finally, it is shown how such insights can be used to propose a general medical intervention based on the use of cerebellar rTMS across the disorder spectrum.

show abstract

Hippocampal dendritic abnormalities in a rat model of phenylketonuria

Lacey

1984

Annals of Neurology

View full text Add to dashboard Cite

An increased concentration of dendritic spines was present in one region of the hippocampus in rats made hyperphenylalaninemic (phenylketonuria model). It is uncertain whether this finding resulted from an actual hyperplasia or a failure of maturational spine reduction. The result is unusual in that Golgi studies of most mental retardation syndromes and relevant animal models have shown loss of dendritic spines.

show abstract

Neuropathology of phenylacetate poisoning in rats: An experimental model of phenylketonuria

Cited by 42 publications

References 45 publications

A Quantitative Ultrastructural Study of the Effects of Phenylacetate on Synaptic Organization in the Developing Rat Cerebral Cortex

A Quantitative Ultrastructural Study of the Effects of Phenylacetate on Synaptic Organization in the Developing Rat Cerebral Cortex

A theory inspired proposal for a novel medical treatment in autism. The cerebellar model of autism and the hypothesis of dorsal stream dysfunction: evidence from idiopathic and syndromic cases.

Hippocampal dendritic abnormalities in a rat model of phenylketonuria

Contact Info

Product

Resources

About